The purpose of this project is to prepare base specific spin label probes to study binding of chemical carcinogens to nucleic acids. For this purpose, we have prepared spin labeled actinomycin-D to probe G-C-regions in nucleic acids. Binding studies with these labels and DNA suggest that these analogs bind to DNA and their DNA-binding modes are similar but not identical to the parent compound. These analogs inhibited DNA-dependent RNA polymerase and were more active than the actinomycin D against P-388 leukemia cells in vivo. In addition, these analogs are more effective in stimulating O2 uptake and the formation of O2- than the parent drug. Sedimentation viscosity measurements suggest that the binding mode is one of intercalation into DNA. DNA-dependent-RNA polymerase studies using various synthetic nucleotide show that these analogs bind only to guanine-cytosine bases in DNA. Electron spin resonance studies suggest that these analogs also bind to cell membranes.